The mutations in DDX3X affect sex-biased cancer occurrence
| Project/Area Number |
16K08673
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Saitama Medical University |
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Principal Investigator |
Momose Shuji 埼玉医科大学, 医学部, 准教授 (70360344)
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| Co-Investigator(Kenkyū-buntansha) |
田丸 淳一 埼玉医科大学, 医学部, 教授 (30188429)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | リンパ腫 / バーキットリンパ腫 / DDX3X / がんの性差 / Burkittリンパ腫 / がん抑制遺伝子 / がん / 性差 / 癌 / 疾患モデル |
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| Outline of Final Research Achievements |
A subset of cancer harbors mutations in DDX3X and we identified DDX3X mutations in B cell lymphoma from our previous genetic screening. Though some types of cancer present sex-bias in its incidence, its underlying mechanism of sex-bias was not elucidated except for the involvement of sex hormone-related cancers. To explore the sex-biased cancer occurrence in the aspect of gene function, we analyzed DDX3X in B cell lymphoma cell lines that harbor DDX3X mutations. Finally we elucidated that wild type DDX3X suppressed PI3K pathway and DDX3X acts as tumor suppressor gene. Also DDX3X located in X-chromosome and reported that it escapes from X chromosomal inactivation. Therefore, the occurrence of DDX3X mutations in male than in female can easily to provoke genetic inactivation as male possess only one X chromosome.
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| Academic Significance and Societal Importance of the Research Achievements |
一部のがん種では男女差がみられるが、性ホルモンが関わるがん種以外では、男女差がなぜ生じるかはわかっていない。本研究では性ホルモンの関与が低いがん種での男女差の機構として、遺伝子の存在する染色体としての性染色体に注目した。
常染色体では通常、2つの相同な遺伝子2つが存在し、がん抑制遺伝子では2つの遺伝子が傷害され初めて機能が喪失する。一方性染色体では、X染色体は女性で2本あるものの男性では1本しかなく、X染色体上に存在するがん抑制遺伝子に関しては男性は女性に比べて遺伝子の機能喪失に陥る可能性が高く、こうした機構ががんの男女差を生じさせている可能性が本研究により示された。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders2019
Author(s)
Tokuhira M, Saito S, Suzuki K, Higashi M, Momose S, Shimizu T, Mori T, Kimura Y, Amano K, Okamoto S, Takeuchi T, Tamaru JI, Kizaki M
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Journal Title
Leuk Lymphoma
Volume: -
Issue: 10
Pages: 1-8
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Human parvovirus B19-induced hemophagocytic lymphohistiocytosis and myocarditis in an adult patient with hereditary spherocytosis2018
Author(s)
Tanaka Y, Takahashi Y, Kimura Y, Tomikawa T, Anan T, Sagawa M, Tabayashi T, Watanabe R, Tokuhira M, Momose S, Tamaru JI, Kizaki M
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Journal Title
Rinsho Ketsueki
Volume: 59
Issue: 6
Pages: 682-687
DOI
NAID
ISSN
0485-1439, 1882-0824
Related Report
Peer Reviewed
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[Journal Article] Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorder, with a focus on regression.2017
Author(s)
Tokuhira M, Saito S, Okuyama A, Suzuki K, Higashi M, Momose S, Shimizu T, Mori T, Anan-Nemoto T, Amano K, Okamoto S, Takeuchi T, Tamaru JI, Kizaki M.
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Journal Title
Leuk Lymphoma
Volume: Sep.10
Issue: 5
Pages: 1-10
DOI
Related Report
Peer Reviewed
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[Journal Article] The aggressive clinical courses of Hodgkin lymphoma primarily diagnosed as methotrexate-induced non-specific lymphoproliferative disorder in patients with rheumatoid arthritis2017
Author(s)
Tokuhira M, Tabayashi T, Tanaka Y, Takahashi Y, Kimura Y, Tomikawa T, Anan-Nemoto T, Momose S, Higashi M, Okuyama A, Watanabe R, Amano K, Tamaru JI, Kizaki M.
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 56
Issue: 3
Pages: 165-169
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed
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